Antimicrobial peptides (AMPs) are ubiquitous in nature and play an important role in the innate immune system of many species (Zasloff, M., Nature (2002) 415:389-395; Epand, R. M., and Vogel, H. J., Biochim Biophys Acta (1999) 1462:11-28). Antimicrobial peptides are diverse in structure, function, and specificity. One major class of antimicrobial peptides consists of linear α-helical peptides, such as cecropin and magainin. Haynie (U.S. Pat. No. 5,847,047) described synthetic peptides based on a heptad repeat and comprised of Leu and Lys residues that were designed to adopt an α-helical amphiphilic structure (see, for example, SEQ ID NO:6); these peptides exhibited activity at 8-63 μg/mL against Escherichia coli and Staphylococcus aureus in solution, however they also exhibited moderate hemolytic activity. Lee, et al. (Biochim. Biophys. Acta (1986) 862:211-219) showed that peptides exhibiting α-helical conformations such as pentapeptide repeat (e.g., (Leu-Leu-Ala-Arg-Leu)3) (SEQ ID NO:7) and tetrapeptide repeat (e.g., (Leu-Ala-Arg-Leu)3 (SEQ ID NO:8) and (Leu-Ala-Arg-Leu)4) (SEQ ID NO:9) peptides had potent antimicrobial activity. In contrast, tri-peptide repeat peptides such as (Ala-Arg-Leu)3 (SEQ ID NO:10) and (Ala-Arg-Leu)4 (SEQ ID NO:11) had weak or no antimicrobial activity.
A need exists for AMPs which exhibit both good antimicrobial activity and reduced hemolytic activity and that can be produced in a cost-effective manner. The present invention provides antimicrobial peptides based on tri-peptide units that exhibit potent antimicrobial activity and reduced hemolytic activity.